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XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

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Lectures<br />

rEGULaTION of aurICIN BIOSYNTHESIS IN<br />

StrePTomyces aureofaCIens CCM 3239<br />

Ján Kormanec, Renáta Nováková, Ľubica Fecková, Peter Kutaš and Alena Reháková<br />

Institute of Molecular Biology, Slovak Academy of Sciences, Dubravska cesta 21,<br />

845 51 Bratislava, Slovakia<br />

Gram-positive bacteria Streptomycetes are the main producers of bioactive natural products<br />

including many antibiotics. The polyketides, which are synthesized by multifunctional<br />

enzymes called polyketide synthase (PKS), belong to the most important classes of antibiotics.<br />

We previously identified a type II polyketide synthase (PKS) gene cluster, aur1, in<br />

Streptomyces aureofaciens CCM3239 with the highest similarity to angucycline polyketide<br />

subgroup of PKS clusters. Deletion of two critical biosynthetic genes resulted in a lack of<br />

antibiotic that was named auricin. However, its purification has been hampered by very<br />

low yields. This cryptic phenotype has been recently described for several homologous<br />

angucycline gene clusters, indicating their tight regulation. Sequence analysis of the<br />

whole aur1 cluster revealed a huge number of regulatory genes, including six genes for<br />

homologues of TetR family repressors, five genes for homologues of specific Streptomyces<br />

Antibiotic Regulatory Proteins (SARP family), a single gene for homologue of AraC/<br />

XylS-family regulators, a single genes for homologue of response regulators of bacterial<br />

two-component signal transduction systems, and two genes for gama-butyrolactone<br />

autoregulator-receptor system. Their partial characterization indicated that several of<br />

them play a positive or negative role in auricin production in a cascade scheme.<br />

Acknowledgements: This work was supported by the Slovak Research and Development<br />

Agency under the contract No. APVV-0017-07.<br />

<strong>XXII</strong>. Biochemistry Congress, Martin<br />

69

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